Ketoconazole proton pump inhibitors

ITRACONAZOLE, KETOCONAZOLE PROTON PUMP INHIBITORS Possible i efficacy of the antifungal L absorption Monitor for i efficacy t dose may be required. Separate doses by at least 2 hours and give ketoconazole with a cola drink... 

Drugs that may be affected by proton pump inhibitors include azole antifungal agents (eg, itraconazole, ketoconazole), benzodiazepines, cilostazol, clarithromycin, digoxin, phenytoin, salicylates, sulfonylureas, and warfarin. Drugs that may affect proton pump inhibitors include sucralfate and clarithromycin. 

Proton pump inhibitors cause a profound and long-lasting inhibition of gastric acid secretion therefore, proton pump inhibitors may interfere with the absorption of drugs where gastric pH is an important determinant of bioavailability (eg, ketoconazole, ampicillin, iron salts, digoxin, cyanocobalamin). 

Drugs that may affect ketoconazole include antacids, didanosine, histamine H2 antagonists, isoniazid, sucralfate, proton pump inhibitors, and rifampin. Drugs that may be affected by ketoconazole include oral anticoagulants, corticosteroids, cyclosporine, protease inhibitors, tricyclic antidepressants, carbamazepine. 

Drugs that may affect atazanavir include the following antacids and buffered medications, clarithromycin, didanosine (buffered formulation only), efavirenz, H2-receptor antagonists, indinavir, itraconazole, ketoconazole, nevirapine, proton pump inhibitors, rifampin, ritonavir, St. John s wort, tenofovir, voriconazole. 

Pantoprazole (Protonix) [Gastric Acid Suppressant/Proton Pump Inhibitor] Uses GERD, erosive gastritis, ZE synd, PUD Action Proton pump inhibitor Dose 40 mg/d PO do not crush/chew tabs 40 mg IV/d (not >3 mg/min, use Protonix filter) Caution [B, /-] Disp Tabs, inj SE Chest pain, anxiety, GI upset Interactions t Effects OF warfarin t effects of photosensitivity W/ St. John s wort X effects OF ketoconazole EMS t Effects of anticoagulants may affect glucose (hypoglycemia) OD Unlikely to cause life-threatening Sxs... 

Rabeprazole (AcipHex) [Antiulcer Agent/Proton Pump Inhibitor] Uses PUD, GERD, ZE H. pylori Action Proton pump inhibitor Dose 20 mg/d may T to 60 mg/d H. pylori 20 mg PO bid X 7 d (w/ amoxicillin and clarithromycin) do not crush/chew tabs Caution [B, /—] Disp Tabs SE HA, fatigue, GI upset Interactions t Effects OF cyclosporine, digoxin -1- effects OF ketoconazole EMS None OD May cause N, tach, dry mouth, and drowsiness symptomatic and supportive... 

Ketoconazole is water-soluble at a pH of below 3. Its oral absorption is influenced by the acidity of the stomach contents, and the concomitant administration of histamine H2 receptor antagonists, proton pump inhibitors, antacids, or food affects its absorption. A high carbohydrate meal ingested with ketoconazole reduces total drug absorption, while a high lipid meal increases it. Erratic absorption is particularly apparent in patients with AIDS. Peak serum concentrations are seen within 2-3 hours. The half-life is about 8 hours. CSF penetration is less than 10% (1). Ketoconazole is extensively metabolized in the liver and excreted in the bile in an inactive form less than 1% of the active drug is excreted in the urine. Clearance is not significantly altered by renal dialysis (1). 

Omeprazole is a proton pump inhibitor. Headache, skin rash, and diarrhea have all been recorded by adverse event registries sufficiently often to suggest causal relations (1). Omeprazole is a modest inhibitor of CYP isoforms. Interactions are less likely than with cimetidine and are probably of no practical importance. However, omeprazole reduces the absorption of drugs that require a low gastric pH (ketoconazole, iron salts, ampicilhn) and can inhibit the hepatic clearance of some drugs (diazepam, warfarin, phenytoin) (2). 

For drugs administered oraUy, impaired gastrointestinal (GI) absorption is an important consideration. For example, aluminum ions in certain antacids or ferrous ions in oral iron supplements form insoluble chelates of tetracycline antibiotics, thereby preventing their absorption. The antifungal ketoconazole is a weak base that is only soluble at acid pH. Drugs that inhibit gastric acidity, such as the proton pump inhibitors and histamine Hj receptor antagonists, impair the dissolution and absorption of ketoconazole. 

Loss of gastric acidity from chronic proton pump inhibitor treatment may affect the bioavailability of such drugs as ketoconazole, ampicillin esters, and iron salts. Chronic therapy, with proton pump inhibitors has been linked to increased frequency of hip fractures, possibly secondary to decreased absorption of calcium. 

Ketoconazole Antacids H2-receptor antagonists Proton pump inhibitors Reduced ketoconazole absorption due to reduced dissolution... 

Ketoconazole is a poorly soluble base, which must be transformed by the acid in the stomach into the soluble hydrochloride salt. Agents that reduce gastric acidity, such as antacids, H2-receptor antagonists , (p.217), and proton pump inhibitors , (p.218), raise the pH in the stomach so that the dissolution of the ketoconazole and its absorption are reduced. Converse-... 

The bioavailability of ketoconazole is reduced by both omeprazole and rabeprazole. Other proton pump inhibitors are expected to behave similarly. Omeprazole also markedly reduces the absorption of itraconazole capsules, but not the oral solution. Proton pump inhibitors are predicted to reduce the bioavailability of posaconazole. The bioavailabilities of fluconazole and voriconazole are not significantly affected by omeprazole. Esomeprazole levels may also be Increased by voriconazole.Omeprazole levels are Increased by ketoconazole, and markedly increased by fluconazole and voriconazole. 

There seem to be no reports about ketoconazole and other proton pump inhibitors but they are also expected to interact to reduce the bioavailability of the ketoconazole, but the extent is not known. 

The interaction between itraconazole and omeprazole also appears to be established, but it appears that this can be minimised by using an oral itraconazole solution. As with ketoconazole, giving itraconazole with an acidic drink such as cola , (p.215) would minimise the interaction, and is recommended by some manufacturers of itraconazole for patients taking proton pump inhibitors. " Monitor patients taking itraconazole if proton pump inhibitors are also given. The effect of itraconazole on omeprazole is unknown, but it might be expeeted to increase omeprazole levels similarly to ketoconazole. 

An active substance, although initially released from its dosage form (and dissolved), may become unavailable for absorption due to reactimis with other medicines or food components [4]. An example is the formation of insoluble complexes of tetracycline with calcium or aluminium ions from antacids or milk products. Interaction (chelation or binding) with iron ions leads to a reduced absorption for a variety of active substances such as doxycycline, penicillamine, methyldopa and ciprofloxacin. The absorption of active substances showing pH-dependent dissolution behaviour may be influenced by medicines that influence the gastric pH, such as H2-antagonists, proton pump inhibitors and antacids. Antimycotic active substances such as ketoconazole or itraconazole dissolve better in acidic fluids. Therefore their bioavailability may be increased by the concomitant use of an acidic drink like cola, whereas the concomitant use of antacids or proton pump inhibitors is likely to reduce the bioavailability. Concomitant use of milk may increase the dissolution of acidic active substances, whereas fats from food may increase the bioavailability of lipophilic active substances like albendazole and griseofulvin. 

Following oral administration, approximately 75% of an administered ketoconazole dose is absorbed. However, there is considerable inter- and intrapatient variation, with oral absorption impaired when gastric acidity is decreased due to clinical pathology, e.g. achlorhydria, or due to concurrent administration of agents that decrease gastric acidity, e.g. antacids, H2-receptor antagonists or proton pump inhibitors, or whether the patient is in a fed or fasted state (absorption is enhanced in the fed state). 

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